DOI:10.2214/AJR.07.2423
AJR 2007; 189:923-927
© American Roentgen Ray Society
Diffusion Tensor Imaging and Tractography of Median Nerve: Normative Diffusion Values
Neslihan Kabakci1,
Bengi Gürses1,
Zeynep Firat1,
Ali Bayram1,
Aziz Müfit Ulu
2,3,
Arzu Kovanlikaya1 and
lhami Kovanlikaya1
1 Department of Radiology, Yeditepe University Hospital, Devlet Yolu Ankara Cad.
102-104, 34752 Kozyatai, Istanbul, Turkey.
2 Department of Biomedical Engineering, Yeditepe University School of
Engineering, Istanbul, Turkey.
3 Department of Radiology, Weill Medical College of Cornell University, New
York, NY.
Received January 29, 2007;
accepted after revision May 13, 2007.
Address correspondence to N. Kabakci
(nkabakci{at}yeditepe.edu.tr).
Preliminary data presented at the 2006 Annual Scientific Meeting of the
European Society for Magnetic Resonance in Medicine and Biology, Warsaw,
Poland.
Abstract
OBJECTIVE. The purposes of this study were to visualize the human
median nerve on diffusion tensor imaging and to determine the normal
fractional anisotropy (FA) value and apparent diffusion coefficient (ADC) of
the normal median nerve.
SUBJECTS AND METHODS. The wrists of 20 healthy volunteers and of two
patients with carpel tunnel syndrome were examined with a 3-T MRI system with
a standard eight-channel sensitivity-encoding head coil. Diffusion tensor
imaging was performed with a spin-echo echo-planar sequence. A T1-weighted
sequence was performed for anatomic reference. After tractography, the FA
value and ADC of the whole nerve were calculated automatically. Manual focal
measurements also were obtained at the levels of the flexor retinaculum,
wrist, and forearm.
RESULTS. We visualized the median nerve with MR diffusion tensor
tractography and followed the nerve for approximately 77.5 mm. We found the
normative diffusion values of the median nerve were an FA of 0.709 ±
0.046 (SD) and an ADC of 1.016 ± 0.129 x 10–3
mm2/s. There was a statistically significant difference between the
FA values obtained at the level of the flexor retinaculum and the values
obtained from the other parts of the median nerve (p < 0.0001). We
found a decrease in FA value (p < 0.01) and an increase in ADC
(p < 0.05) with advancing age.
CONCLUSION. The normative diffusion values of the human median nerve
can be used as a reference in evaluation, diagnosis, and follow-up of
entrapment, trauma, and regeneration of the median nerve.
Keywords: diffusion tensor imaging • median nerve • MRI
Introduction
The median nerve is one of three main nerves of the forearm. It arises from
the lateral and medial cords of the brachial plexus (C6–T1). At the
wrist level, it passes under the flexor retinaculum deep in relation to the
flexor digitorum superficialis tendons through the carpal tunnel and divides
into digital and muscular branches distal in relation to the flexor
retinaculum. Several entrapment and compression syndromes affect these nerves
of the forearm. Carpal tunnel syndrome (CTS) is the most common peripheral
neuropathy of the upper extremity resulting from dysfunction of the median
nerve. CTS is characterized by numbness in the first three digits and the
radial aspect of the fourth digit and by thenar atrophy. There are several
diagnostic methods for CTS, such as the Phalen maneuver, Flick test, and
electromyography [1,
2]. Although the sensitivity
and specificity of MRI in the diagnosis of CTS are low (sensitivity,
23–96%; specificity, 39–87%), a few signs, such as nerve
enlargement, nerve flattening, and increased nerve signal intensity, do occur
[1].
With application of the appropriate magnetic field gradients, MRI can be
sensitized to the thermally driven random motion (diffusion) of water
molecules in the direction of the field gradient. This technique is called
diffusion-weighted imaging (DWI)
[3]. Many materials have
intrinsic structural properties that hinder diffusion so that diffusivity is
greater in some directions than in others. This property is known as
anisotropy. If there is no directional variation in diffusion rate, diffusion
is said to be isotropic. Biologic tissues often are anisotropic because
structures such as cell membranes and large protein molecules restrict the
motion of water molecules. This property is called restricted diffusion. DWI
usually shows diffusion information in one direction. In an anisotropic
sample, diffusion tensor imaging (DTI) is required to fully characterize
diffusion. In theory, to determine all elements of the diffusion tensor, at
least six independent measurements with diffusion gradients applied
sequentially along six noncollinear directions are required
[4–7].
The direction of maximum diffusivity has been shown to coincide with the fiber
tract orientation [6,
7]. In white matter fiber
bundles, water molecules move more along the fibers than in other directions
[8]. With special fiber
tracking software, it is possible to visualize neural tracts with DTI data
[3].
Peripheral nerve imaging can be useful in the diagnosis of nerve
compression, inflammation, trauma, and neuropathy and in the postoperative
follow-up of nerve repair procedures. MR neurographic methods with
fat-saturated heavily T2-weighted sequences or STIR T2-weighted sequences also
can be used for peripheral nerve imaging
[9]. DTI has been used mostly
in imaging of the CNS to visualize white matter tracts. Several studies
[10–12]
have shown the clinical applications of DTI in neuronal disorders such as
stroke, epilepsy, and CNS tumors. In a few studies
[8,
12,
13], peripheral nerves have
been visualized with DTI. For use of DTI in the diagnosis of pathologic
conditions affecting peripheral nerves, the normative values of these nerves
must be determined. In this study, our aims were to visualize the human median
nerve with DTI and to determine the normal fractional anisotropy (FA) value
and apparent diffusion coefficient (ADC) for use in the diagnosis of CTS, the
most common peripheral neuropathy.
Subjects and Methods
Imaging was performed on the wrists of 21 volunteers (six men, 14 women;
mean age, 27.5 years; range, 21–35 years) with no history of medication
use, surgery, or neurologic disorder related to the median nerve. Informed
consent was obtained from all subjects. We also imaged the wrists of two
patients with CTS to explore the applicability of the method to pathologic
conditions. The examinations were performed on a 3-T MRI system (Intera
Achieva, Philips Medical Systems) with a maximum gradient amplitude of 30
mT/m, slew rate of 150 T/m/s, and an eight-channel sensitivity-encoding head
coil. During imaging, the coil was positioned in the center of the magnet
bore. The subject was in a prone position with the hands over the head within
the coil and immobilized with cushions, sandbags, and bandages. This
positioning produced little discomfort for the subjects.
A single-shot spin-echo echo-planar DTI sequence was used with the
following parameters: TR/TE, 4,600/90; flip angle, 90°; field of view, 140
mm; matrix size, 128 x 128; number of signals averaged, 3. Diffusion
weighting with a b value of 1,000 s/mm2 was applied in 32
directions. An image without diffusion gradients also was acquired. Total
sequence duration was 7 minutes 49 seconds. The data were obtained from 35
axial slices of 4-mm thickness with no gap. For anatomic reference, a
T1-weighted axial sequence was obtained (382/20; flip angle, 90°; field of
view, 140 mm; number of signals averaged, 2).
After DTI data were transferred to a PC, manufacturer-supplied software
(PRIDE, Philips Medical Systems) was used for fiber tracking. The first step
was to use color-coded maps in the coronal plane to locate the nerve
(Fig. 1A). Circular regions of
interest (ROIs) were placed in the anatomic location of the median nerve
expected on the basis of information from coronal and axial color-coded maps
(Fig. 1B). ROI placement was
done at two levels: the distal radioulnar joint and one of the most proximal
slices. The locations of the coded fibers were confirmed by use of the
anatomic location on T1-weighted reference images
(Fig. 1C). A circular ROI
larger than the nerve was used for this purpose
(Fig. 2A). The anisotropy
threshold was 0.3. After anatomic confirmation of the median nerve tract, the
number of coded fibers, mean fiber length, mean FA value, and mean ADC were
calculated with the software. The ADC calculated was one third of the trace of
the diffusion tensor.
On the color-coded map, three points along the tract of the median nerve in
the axial and coronal planes were determined for focal FA measurements. One of
the measurements was obtained at the level of flexor retinaculum. The other
measurements were obtained at the wrist and forearm levels. At the wrist
level, FA was measured from the median nerve at the level of musculotendinous
junctions of the flexor digitorum and palmaris longus muscles. At the forearm
level, the measurement was obtained approximately 5 cm proximal to the flexor
retinaculum in the center of the flexor digitorum muscle bundles. For these
measurements, ROIs smaller than the nerve were selected to avoid partial
volume effects (Fig. 2B).
Statistical analyses were performed with commercially available software
(SPSS 11.0, SPSS).
The mean FA values and ADCs obtained from the whole median nerve and focal
measurements were compared by Friedman variance analysis and Wilcoxon's signed
rank test. The comparison of FA values and ADCs on the basis of age was
evaluated with Spearman's rank correlation test. A value of p <
0.05 was considered significant.
Results
The images of three of the 21 volunteer subjects were initially discarded
because of the presence of motion artifacts. We repeated imaging of two of
these subjects and included their data in the analysis. As a result, the
median nerves of 20 subjects were visualized with DTI and fiber tracking.
Figures 3,
4,
5,
6 show the tractographic images
of the median nerves of selected subjects.
The number and length of the tracked fibers, mean FA value, and mean ADC
are summarized in Table 1. The
mean number of tracked fibers was 1,417, and the mean length was 77.5 mm
(range, 52.86–100.40 mm). The FA values of the normal median nerve
ranged from 0.69 to 0.80. The mean FA value for all of the subjects was 0.709
± 0.046 (SD). The ADCs of normal median nerves were between 0.74 and
1.27 x 10–3 mm2/s. The mean ADC was 1.016
± 0.129 x 10–3 mm2/s. The mean FA
value was 0.72 ± 0.05 for the women and 0.69 ± 0.01 for men. The
mean ADC for the women was 0.97 ± 0.10 and that for the men was 1.12
± 0.12. There was no statistically significant difference between the
values for men and those for women. There were, however, significant
differences with advancing age: a significant increase in ADC (Spearman's rank
correlation, p < 0.05; 
= 0.547) and a significant decrease
in FA value (Spearman's rank correlation, p <0.01; =
0.726).
View this table:
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TABLE 1: Number and Length of Tracked Fibers, Mean Fractional Anisotropy Value,
and Mean Apparent Diffusion Coefficient for Median Nerves (n =
20)
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The mean FA value and ADC of focal measurements of the median nerve at the
flexor retinaculum, wrist, and forearm levels are shown in
Table 2. At the flexor
retinaculum level, the mean FA value was 0.59 ± 0.07 and the mean ADC,
0.97 ± 0.03 x 10–3 mm2/s. At the
wrist level, the mean FA value was 0.72 ± 0.07 and the mean ADC, 0.95
± 0.02 x 10–3 mm2/s. At the forearm
level, the mean FA value was 0.71 ± 0.08 and the mean ADC, 0.98
± 0.02 x 10–3 mm2/s. There was a
statistically significant difference between the FA value obtained from the
flexor retinaculum level and those obtained from the other parts of the median
nerve (p < 0.0001). No statistical difference was observed between
ADCs measured at the three anatomic locations. In the two patients with CTS,
the mean FA values of the median nerve were 0.41 and 0.44. These values were
both 2 SDs below the normal value.
Discussion
DTI has been used mostly in visualization of white matter fibers in the CNS
[7]. The results of our study
show that DTI and fiber tracking at 3 T can be used to visualize the
peripheral nerves. In a study with three healthy volunteers, Skorpil et al.
[14] used DTI with fiber
tracking on a 1.5-T MRI system to image the sciatic nerves in vivo. Hiltunen
et al. [8] later used a 3-T MRI
system to study the median, ulnar, and radial nerves and the tibial and
peroneal nerves of six healthy subjects. Meek et al.
[13] were the first to image
abnormalities in the peripheral nerve with DTI. In a postoperative evaluation
3 months after fascicular nerve repair, those authors visualized the median
nerve, which could be tracked only up to the transection site 1 month after
the procedure. That report showed DTI to be capable of depicting living nerve
fibers. Further prospective large series are needed, however, to assess the
value of DTI in nerve repair surgery.
Several indexes can be used for quantitative analysis of DWI and DTI data.
We used ADC and FA value. ADC is a scalar value reflecting molecular
diffusivity under motion restriction and is independent of magnetic field
strength [8,
15,
16]. Like T1- and T2-weighted
relaxation, diffusivity is thought to be an intrinsic tissue parameter and has
been used primarily in the diagnosis of acute cerebral ischemia
[5]. The other parameter, FA
value, is one of the most common anisotropy metrics. It ranges from 0 to 1,
where 0 is isotropic and 1 is fully anisotropic. The direction of maximum
diffusivity is mapped with red, green, and blue color coding in which
brightness is modulated by FA. The result is a summary map from which the
degree of anisotropy and local fiber direction can be determined
[7].
In our study, the normal FA value and ADC of the median nerve were defined.
To our knowledge, only one study
[9] has shown the FA value and
ADC of this nerve. In that study, the FA values of four subjects were between
0.69 and 0.89, and the ADCs ranged from 0.94 to 1.36 x
10–3 mm2/s. In our study, the whole median nerve
tract had a mean FA value of 0.709 ± 0.046 and a mean ADC of 1.016
± 0.129 x 10–3 mm2/s. We believe that
these normative values may play an important role in the diagnosis of CTS
because, as shown in this study, focal FA measurement of the nerve at the
flexor retinaculum level showed a significant difference from values at other
levels. Under the flexor retinaculum, the position of the median nerve is
constant among the flexor tendons. Therefore, the motion of water molecules
through the myelin sheath can be affected, causing FA values to vary. By a
similar mechanism, CTS also can cause a change in FA values.
FA values can aid in follow-up after nerve repair procedures. We found that
although there was a difference in FA values, ADCs did not differ
significantly in different parts of the median nerve. This finding shows that
diffusion anisotropy indexes may be more sensitive than ADC in the evaluation
of nerves for pathologic conditions. In the two patients with CTS in this
study, we found the mean FA values of human median nerve were 0.41 and 0.44,
both 2 SDs below the normal value.
In this study, the age-related change in anisotropy indexes found in the
median nerve was similar to previously reported age-related anisotropy changes
in the brain [17,
18]. Although the oldest
subject in our study was only 35 years old, we observed that with increasing
age, FA value in normal human median nerves decreased (p < 0.01)
and ADC increased (p > 0.05). A decrease in the number of
myelinated fibers in the peripheral nerve with advancing age has been reported
[19,
20]. A progressive age-related
decrease in conduction velocity of the median nerve after the age of 20 years
also has been reported [20,
21]. We believe that the
changes in FA value and ADC may be associated with the decrease in fiber
number with advancing age. These results indicate that patient age may have to
be considered in comparing the anisotropy indexes of healthy subjects with
those of persons with peripheral nerve disorders. Age-matched control groups
may be necessary in such studies.
Imaging of the peripheral nerves with DTI is thought to have difficulties
such as differentiating the nerves from surrounding structures such as
ligaments and muscles. Because muscle fibers are shorter than nerve fibers and
have a relatively low anisotropy index, this difficulty can be overcome with
use of fiber length and degree of anisotropy
[8]. For this purpose, we set
the anisotropy threshold at 0.3. The color-coded maps, especially in the
coronal plane, combined with anatomic reference views made it easy to localize
median nerve tracts.
There are several disadvantages to the technique used. The major limitation
is a relatively long data acquisition time, which makes the sequence more
susceptible to motion artifacts. Especially in postoperative follow-up, image
degradation due to motion artifacts can be a serious problem because of the
uncomfortable positioning for median nerve visualization. Another limitation
is that spatial resolution is low, even with a 3-T MRI system. In our study,
the in-plane resolution was 1.09 x 1.09 mm2, which can be
improved with dedicated wrist coils.
In conclusion, we found that in DTI of 20 healthy subjects, the FA value of
normal median nerve was 0.709 ± 0.046 and the ADC was 1.016 ±
0.129 x 10–3 mm2/s. Our findings suggest
that FA value and ADC can be used in the diagnosis of CTS because focal FA
measurement of the nerve at the flexor retinaculum level showed a significant
difference from FA values in other parts of the nerve. Age-related changes in
anisotropy also should be taken into account in evaluation of the median
nerve.
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Abstract
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